Immune hub genes and a proof-of-concept prognostic signature in EBV-associated gastric carcinoma

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) represents a distinct molecular subtype with unique immune characteristics but lacks subtype-specific prognostic tools for clinical management. We developed an immune-based prognostic signature by integrating transcriptomic profiling, immunohistochemical validation, and functional assays. PTPRC (CD45) and ITGB2 (CD18) were identified as central immune regulators with strong correlation (r = 0.78, p < 0.001) and significant enrichment in EBVaGC (CD45⁺ and CD18⁺: 6907 vs. 2876 and 542 vs. 160 cells/mm², both p < 0.0001), co-localizing with CD68⁺ macrophages. The four-gene Immunoscore demonstrated robust risk stratification (C-index = 0.922; hazard ratio = 24.6, p = 0.002) and maintained discrimination in independent validation (C-index = 0.765; hazard ratio = 8.68, p = 0.0023). Functional assays confirmed CD18's role in monocyte migration (62.6% reduction upon blockade, p < 0.001). This exploratory study establishes an immune-based prognostic model for EBVaGC, with potential to guide risk-adapted surveillance and immunotherapy selection pending multi-center validation.